Ovary Development

Embryology - 5 Dec 2023        Expand to Translate
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Introduction

Adult human ovary viewed by endoscopy

The female gonad is the ovary and is closely associated with female internal genital (reproductive) tract development. In humans, these laterally paired organs lie within the peritoneal cavity. Genes such as WNT-4 and DAX-1 necessary for initiation of female pathway ovary development, female gonad is not considered a default process.

Initial gonad development in females and males is virtually identical with germ cells migrating into an indifferent gonad. In females with XX, the ovary then begins to develop and the subsequent structure and timecourse of germ cell then differs between males and females. In the ovary oocytes proliferate prior to birth and arrest in meiosis 1.

Historic Embryology

Regnier de Graaf (1641 – 1673) was a Dutch anatomist and physician who described the anatomy of the uterine tube and the development of follicles in the ovary. He was first to describe the "Graafian follicle" (preovulatory follicle) in the ovary of mammals, but erroneously believed the entire follicle to be the mammalian oocyte (egg).

Links: menstrual cycle | oocyte | X Chromosome | AMH | PCOS | ovarian reserve | Category:Ovary | Category:Oocyte

Genital Links: genital | Lecture - Medicine | Lecture - Science | Lecture Movie | Medicine - Practical | primordial germ cell | meiosis | endocrine gonad‎ | Genital Movies | genital abnormalities | Assisted Reproductive Technology | puberty | Category:Genital Female | X | X inactivation | ovary | corpus luteum | oocyte | uterus | vagina | reproductive cycles | menstrual cycle | Category:Female Male | Y | SRY | testis | spermatozoa | ductus deferens | penis | prostate | Category:Male

Historic Embryology - Genital  General: 1901 Urinogenital Tract | 1902 The Uro-Genital System | 1904 Ovary and Testis | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1921 Urogenital Development | 1921 External Genital | 1942 Sex Cords | 1953 Germ Cells | Historic Embryology Papers | Historic Disclaimer Female: 1904 Ovary and Testis | 1904 Hymen | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1914 Female | 1921 External Genital | 1927 Female Foetus 15 cm | 1927 Vagina | 1932 Postnatal Ovary Male: 1887-88 Testis | 1904 Ovary and Testis | 1904 Leydig Cells | 1906 Testis vascular | 1909 Prostate | 1912 Prostate | 1914 External Genitalia | 1915 Cowper’s and Bartholin’s Glands | 1920 Wolffian tubules | 1935 Prepuce | 1935 Wolffian Duct | 1942 Sex Cords | 1943 Testes Descent | Historic Embryology Papers | Historic Disclaimer

Some Recent Findings

Human ovarian reserve study design

Testosterone metabolism

Two distinct pathways of pregranulosa cell differentiation support follicle formation in the mouse ovary DOI "We sequenced more than 52,500 single cells from embryonic day 11.5 (E11.5) postembryonic day 5 (P5) gonads and performed lineage tracing to analyze primordial follicles and wave 1 medullar follicles during mouse fetal and perinatal oogenesis. Germ cells clustered into six meiotic substages, as well as dying/nurse cells. Wnt-expressing bipotential precursors already present at E11.5 are followed at each developmental stage by two groups of ovarian pregranulosa (PG) cells. One PG group, bipotential pregranulosa (BPG) cells, derives directly from bipotential precursors, expresses Foxl2 early, and associates with cysts throughout the ovary by E12.5. A second PG group, epithelial pregranulosa (EPG) cells, arises in the ovarian surface epithelium, ingresses cortically by E12.5 or earlier, expresses Lgr5, but delays robust Foxl2 expression until after birth. By Template:ME19.5, EPG cells predominate in the cortex and differentiate into granulosa cells of quiescent primordial follicles. In contrast, medullar BPG cells differentiate along a distinct pathway to become wave 1 granulosa cells. Reflecting their separate somatic cellular lineages, second wave follicles were ablated by diptheria toxin treatment of Lgr5-DTR-EGFP mice at E16.5 while first wave follicles developed normally and supported fertility. These studies provide insights into ovarian somatic cells and a resource to study the development, physiology, and evolutionary conservation of mammalian ovarian follicles." Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells "The human ovary orchestrates sex hormone production and undergoes monthly structural changes to release mature oocytes. The outer lining of the ovary (cortex) has a key role in defining fertility in women as it harbors the ovarian reserve. It has been postulated that putative oogonial stem cells exist in the ovarian cortex and that these can be captured by DDX4 antibody isolation. Here, we report single-cell transcriptomes and cell surface antigen profiles of over 24,000 cells from high quality ovarian cortex samples from 21 patients. Our data identify transcriptional profiles of six main cell types; oocytes, granulosa cells, immune cells, endothelial cells, perivascular cells, and stromal cells. Cells captured by DDX4 antibody are perivascular cells, not oogonial stem cells. Our data do not support the existence of germline stem cells in adult human ovaries, thereby reinforcing the dogma of a limited ovarian reserve." neural crest-derived neurons invade the ovary but not the testis during mouse gonad development "Testes and ovaries undergo sex-specific morphogenetic changes and adopt strikingly different morphologies, despite the fact that both arise from a common precursor, the bipotential gonad. Previous studies showed that recruitment of vasculature is critical for testis patterning. However, vasculature is not recruited into the early ovary. Peripheral innervation is involved in patterning development of many organs but has been given little attention in gonad development. In this study, we show that while innervation in the male reproductive complex is restricted to the epididymis and vas deferens and never invades the interior of the testis, neural crest-derived innervation invades the interior of the ovary around E16.5. Individual neural crest cells colonize the ovary, differentiate into neurons and glia, and form a dense neural network within the ovarian medulla. Using a sex-reversing mutant mouse line, we show that innervation is specific to ovary development, is not dependent on the genetic sex of gonadal or neural crest cells, and may be blocked by repressive guidance signals elevated in the male pathway." neural crest Establishment and characterization of human theca stem cells and their differentiation into theca progenitor cells "In this study, we have characterized the human theca stem cells (hTSCs) and their differentiation into human theca progenitor cells (hTPCs). hTSCs were isolated from the theca layer of small antral follicles (3-5 mm in size)." ovary

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Ovary Development | Ovarian Follicle Development | Folliculogenesis | Ovulation | Primordial Follicle | Graafian Follicle | Ovarian Reserve | Cumulus-Oocyte Complex

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. Reelin and aromatase cooperate in ovarian follicle development "Reelin plays an important role in cerebral cortex development and synaptogenesis. In the hippocampus, the neurosteroid estrogen affects reelin expression. ...Our data provide evidence of a local increase of aromatase expression by reelin. Regarding reproduction, this crosstalk may contribute to follicular stability and counteract luteinization in ovaries." Review - polycystic ovary syndrome "This article aims to provide a balanced review of the latest advances and current limitations in our knowledge about PCOS while also providing a few clear and simple principles, based on current evidence-based clinical guidelines, for the proper diagnosis and long-term clinical management of women with PCOS." Quantitative proteomic profiling human ovary from early to mid-gestation "Here, quantitative mass spectrometry was conducted on ovarian tissue collected at key stages during the first two trimesters of human gestational development, confirming the expression profiling data using immunofluorescence as well as in-vitro modeling with human oogonial stem cells (OSCs) and human embryonic stem cells (ESCs). A total of 3,837 proteins were identified in samples spanning developmental days 47-137. Bioinformatics clustering and Ingenuity Pathway Analysis identified DNA mismatch repair and base excision repair as major pathways upregulated during this time. Additionally, MAEL and TEX11, two key meiosis-related proteins, were identified as highly expressed during the developmental window associated with fetal oogenesis." Review - Role of androgens in the ovary "It has been well established for decades that androgens, namely testosterone (T) plays an important role in female reproductive physiology as the precursor for oestradiol (E2). However, in the last decade a direct role for androgens, acting via the androgen receptor (AR), in female reproductive function has been confirmed. Deciphering the specific roles of androgens in ovarian function has been hindered as complete androgen resistant females cannot be generated by natural breeding. In addition, androgens can be converted into estrogens which has caused confusion when interpreting findings from pharmacological studies, as observed effects could have been mediated via the AR or estrogen receptor. The creation and analysis of genetic mouse models with global and cell-specific disruption of the Ar gene, the sole mediator of pure androgenic action, has now allowed the elucidation of a role for AR-mediated androgen actions in the regulation of normal and pathological ovarian function." Retransplantation of cryopreserved ovarian tissue: the first live birth in Germany "Cryopreserved ovarian tissue can be retransplanted to restore fertility after radiation or chemotherapy. To date, 15 live births after retransplantation have been reported worldwide. We report the first pregnancy and the first live birth after retransplantation in Germany. This was the first live birth after retransplantation of cryopreserved ovarian tissue in Germany and also the first case with histological confirmation that the oocyte from which the patient conceived could only have come from the retransplanted tissue." Mammalian ovary differentiation - A focus on female meiosis "Over the past 50 years, the ovary development has been subject of fewer studies as compare to the male pathway. Nevertheless due to the advancement of genetics, mouse ES cells and the development of genetic models, studies of ovarian differentiation was boosted. This review emphasizes some of new progresses in the research field of the mammalian ovary differentiation that have occurred in recent years with focuses of the period around prophase I of meiosis and of recent roles of small non-RNAs in the ovarian gene expression." Human RSPO1/R-spondin1 is expressed during early ovary development and augments β-catenin signaling "Human testis development starts from around 42 days post conception with a transient wave of SRY expression followed by up-regulation of testis specific genes and a distinct set of morphological, paracrine and endocrine events. Although anatomical changes in the ovary are less marked, a distinct sub-set of ovary specific genes are also expressed during this time. The furin-domain containing peptide R-spondin1 (RSPO1) has recently emerged as an important regulator of ovary development through up-regulation of the WNT/β-catenin pathway to oppose testis formation. Here, we show that RSPO1 is upregulated in the ovary but not in the testis during critical early stages of gonad development in humans (between 6-9 weeks post conception), whereas the expression of the related genes WNT4 and CTNNB1 (encoding β catenin) is not significantly different between these tissues. Furthermore, reduced R-spondin1 function in the ovotestis of an individual (46,XX) with a RSPO1 mutation leads to reduced β-catenin protein and WNT4 mRNA levels, consistent with down regulation of ovarian pathways"

Human Ovary Timeline

Fetal gonad retinoid receptor expression

Approximate Timeline of human development listed below.

Human Ovary Timeline

Time	Carnegie Stage	Event
24 days	11	intermediate mesoderm, pronephros primordium
28 days	12	mesonephros and mesonephric duct
35 days	14	uteric bud, metanephros, urogenital ridge
42 days	17	cloacal divison, gonadal primordium (indifferent)
49 days	19	paramesonephric duct, gonadal differentiation
6-7 weeks (GA 8-9 weeks)		primordial germ cell mitosis proliferation commences
56 days	23	paramesonephric duct fusion (female)
12-14 weeks (GA 14-16 weeks)	fetal	primordial germ cell meiosis germ cell differentiation, formation of syncitial clusters of oogonia
15-18 weeks (GA 17–20 weeks)	fetal	breakdown of syncitial clusters and assembly of primordial follicles
Links: ovary | oocyte | timeline | Category:Timeline

Movies

‎‎Ovary Page | Play

‎‎Urogenital Septum Page | Play

‎‎Female External‎‎ Page | Play

‎‎Uterus Page | Play

Mouse Primordial Germ Cell Migration
‎‎Germ Cell E9.0 Page | Play	‎‎Germ Cell E9.5 Page | Play	‎‎Germ Cell E10.5 Page | Play

Oogenesis

The 2 human ovaries gradually lose follicles both before and after puberty (the beginning of ovulation); beginning with about several million before birth, maximum number at birth, 300-400,000 by puberty and finally by late 40’s have only a few follicles left. Recent studies suggest that the original calculations of ovary follicle numbers at birth were over-estimates and the actual figure should be about 2.5 million. The number of antral follicles detected within the ovary also decreases with increasing maternal age. In humans, a primodial follicle take about 150 days to develop into a preantral follicle (primary) and another 120 days to form an antral follicle (secondary). A number of antral follicles will then "compete" for 14-15 days to become the dominant follicle, which will undergo ovulation. ovarian reserve - Clinical term for the number of oocytes (non-growing follicles) available for possible fertilization at the different times during female reproductive life. A blood test for Anti-Mullerian Hormone (AMH) levels is used clinically as a measure of the ovarian reserve.

Human ovary non-growing follicle model

Cumulus-Oocyte Complex - (COC) Clinical term used in Assisted Reproductive Technology to describe the ovulated Graafian follicle consisting of the oocyte surrounded by a packed layers of cumulus cells.

Fetal Ovary

Fetal human ovary meiosis (second trimester) H2AFX and SYCP3 are meiotic markers

Infant Ovary

Overview	Follicle

This image shows a region (see inset) of the infant ovary cortex.

There are a large number of developing oocytes which will eventually form a dense primordial germ layer at the ovary periphery.

Later stages of follicle development are completely absent and will begin to only appear just prior to puberty.

Table showing the Growth of the Ovary
Vertex-breech length	Greatest diam. of head	Right Ovary		Left Ovary		Comparison between
		Breadth	Length	Breadth	Length	Length		Breadth
						R.	L.	R.	L.
50.0	42.6	0.9	1.9	0.9	2.5	..	+	—	—
125.0	123.0	1.2	5.9	1.5	4.1	+	..	..	+
138.0	115.0	1.6	5.0	2.0	5.0	—	—	..	+
156.0	131.0	1.9	7.2	2.0	7.1	+	..	..	+
173.0	163.5	3.0	9.0	...	...	..	..	..	..
190.0	175.0	2.9	7.7	2.1	7.8	..	+	+	..
223.0	162.0	2.9	10.5	3.0	9.1	+	..	..	+
235.0	190.0	4.2	10.0	3.8	12.0	..	+	+	..
260.0	213.0	3.6	11.1	4.0	11.4	..	+	..	+
272.0	213.0	3.0	10.0	3.5	9.2	+	..	..	+
305.0	238.0	3.0	9.9	3.9	10.9	..	+	..	+
347.0	...	3.5	10.8	4.9	8.5	+	..	..	+
355.0	273.0	4.0	14.0	5.2	9.9	+	..	..	+
386.0	324.0	5.1	11.5	3.0	9.9	+	..	+	..
402.0	301.0	5.05	10.5	3.0	12.0	..	+	+	..
3 weeks	...	5.0	17.0	5.0	14.0	+	..	—	—
6 weeks	...	7.5	15.0	7.0	14.7	+	..	+	..
6 weeks	...	7.0	18.0	8.0	17.0	+	..	..	+
10 weeks	...	...	14.0	...	16.0	+	..	—	—
2 months	...	6.0	14.5	4.0	13.0	+	..	+	..
3 months	...	6.0	15.5	5.0	14.7	+	..	+	..
7 months	...	5.9	15.5	4.5	18.1	..	+	+	..
15 months	...	9.0	18.0	9.0	19.5	+	..	—	—
I.75 years	...	7.0	20.0	8.5	15.0	+	..	..	+
4 years	...	10.0	27.0	12.7	23.2	+	..	..	+
5.5 years	...	11.1	29.0	9.1	26.1	+	..	+	..
14 years	...	11.9	26.5	12.0	29.5	..	+	..	+
The measurements are all given in millimeters, breech length is measured along the nape and the back.
Reference: Felix W. The development of the urinogenital organs. In Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia. pp 752-979.
Links: 1912 Ovary Growth | Table Ovary Growth Table | Collapsible Table | Ovary Development

Ovarian Reserve

Human ovarian reserve study design

Ovarian Reserve - Clinical term for the number of oocytes (non-growing follicles) available for possible fertilization at the different times during female reproductive life. A blood test for Anti-Mullerian Hormone (AMH) levels is used clinically as a measure of the ovarian reserve. A negative finding has been described as Diminished Ovarian Reserve, or an ovarian insufficiency or premature ovarian failure and may be seen in adult childhood cancer survivors and adult patients undergoing a number of therapies.

The dogma in human (mammalian) development is that new oocyte and follicle production does not occur during postnatal life. A recently published human ovary molecular study has reinforced this dogma. There is also substantial data that shows human ovarian changes postnatally are loss by apoptosis of prenatal oocytes.

Alternative Theories

Postnatal Generation - A research group (Tilly JL, Johnson J. 2004, 2007) has published experiments using mice, showing potentially other sources/sites (bone marrow) of oocyte (putative germ cell) generation. They recently stated that the argument should be based upon "experimental approaches than simply an absence of evidence, especially from gene expression analyses". Several other research groups (Eggan K etal. 2004 and Veitia etal. 2007) have argued against these findings.

Links: Image - human follicle number | Assisted Reproductive Technology | oocyte | Search PubMed - Ovarian Reserve | Search PubMed - Diminished Ovarian Reserve

Adult Follicle Structure

Secondary (Antral) Follicle Structure

A follicle usually contains a single oocyte (egg, ovum, female gamete) and a series of supporting cells and a single fluid-filled space in layers surrounding this cell. The 3 layers below are arranged in layers outward from the oocyte.

Granulosa Cells

• A specific cell type that proliferates in association with the oocyte within the developing follicles of the ovary. These cells form the follicle stratum granulosa and are also given specific names based upon their position within the follicle.
• With development of the antral follicle, there are two populations of granulosa cells with distinct characteristics and functions: mural granulosa cells and cumulus cells.
  • mural granulosa cells - an endocrine role by producing steroid hormones and various other ligands
  • cumulus cells - play a support role for oocyte development

Alternate Histological Terms

• • The membrana granulosa cells sit on the follicular basal lamina and line the antrum as a stratified epitelium. Following ovulation, these granulosa cells contribute to corpus luteum.
  • The cumulus oophorus is a column of granulosa cells that attaches the oocyte to the follicle wall. At ovulation, this column of cells is broken or separates to release the oocyte from its follicle attachment.
  • The corona radiata are the granulosa cells that directly surround the oocyte, and are released along with it at ovulation. Following ovulation, the corona radiata provide physical protection to the oocyte and are the initial structural barrier that spermatazoa must penetrate during fertilization.

Links: granulosa cell

Follicular Fluid

• The antrum is a fluid-filled space in the secondary (antral) follicle
• At ovulation, fluid is released along with the oocyte
• Thought to "carry" the oocyte out of the follicle (like a boat on a wave)
• Aids entry into the uterine tube

Theca Interna

(Greek, thek = box) The ovarian follicle endocrine cells forming the inner layer of the theca folliculi surrounding the developing follicle within the ovary. This vascularized layer of cells respond to leutenizing hormone (LH) synthesizing and secreting androgens (androstendione) transported to glomerulosa cells which process initially into testosterone and then by aromatase into estrogen (estradiol). Theca cells do not begin hormonal functions until puberty.

Theca Externa

(Greek, thek = box) The ovarian follicle stromal cells forming the outer layer of the theca folliculi surrounding the developing follicle within the ovary. Consisting of connective tissue cells, smooth muscle and collagen fibers.

Follicle Classification

There are several different nomenclatures for the stages of follicle maturation. It probably does not matter which naming system you use, as long as you are consistent and use the same set of terminology for all stages. Early stages of follicle development appear to be gonadotropin (Gn) independent and with development become gonadotropin "sensitive" and then "dependent" . (UK spelling is gonadotrophin).

Follicle development stages and the relationship to gonadotropin (Gn)]]

Human ovary follicle development

Human Ovarian Follicle Classification

Class	Alternate nomenclature	Type	Number of Cells	Size (diameter µm)	Size ultrasound (mm)
primordial follicle	small	1, 2, 3	25	less than 50
primary follicle	preantral	4 5	26 - 100 101 - 300	up to 200
secondary follicle	antral small antral large antral	6 7	3001 - 500 501 - 1000	500 1000 - 6000	less than 18
preovulatory follicle	Graafian	8	greater than 1000	greater than 6000	18 – 28
Links: ovary | oocyte | menstrual cycle

Primordial Follicle

Human Follicle Classification
Follicle Class	Alternate nomenclature	Type	Number of Cells	Size (diameter µm)
Primordial	small	1, 2, 3	25	less than 50

Human Ovarian Follicle Classification
Class	Alternate nomenclature	Type	Number of Cells	Size (diameter µm)	Size ultrasound (mm)
primordial follicle	small	1, 2, 3	25	less than 50
primary follicle	preantral	4 5	26 - 100 101 - 300	up to 200
secondary follicle	antral small antral large antral	6 7	3001 - 500 501 - 1000	500 1000 - 6000	less than 18
preovulatory follicle	Graafian	8	greater than 1000	greater than 6000	18 – 28
Links: ovary | oocyte | menstrual cycle

Primate primordial follicles (Stain - Haematoxylin Eosin). Note the single layer of follicle cells surrounding the oocyte.

Electron Micrograph of a human oocyte in a primordial follicle. Most of the organelles are concentrated in one pole of the oocyte.

Primary Follicle

Human Follicle Classification
Follicle Class	Alternate nomenclature	Type	Number of Cells	Size (diameter µm)
Primary	preantral	4 5	26 - 100 101 - 300	up to 200

Human Ovarian Follicle Classification
Class	Alternate nomenclature	Type	Number of Cells	Size (diameter µm)	Size ultrasound (mm)
primordial follicle	small	1, 2, 3	25	less than 50
primary follicle	preantral	4 5	26 - 100 101 - 300	up to 200
secondary follicle	antral small antral large antral	6 7	3001 - 500 501 - 1000	500 1000 - 6000	less than 18
preovulatory follicle	Graafian	8	greater than 1000	greater than 6000	18 – 28
Links: ovary | oocyte | menstrual cycle

Histological image of a primary follicle.

Secondary Follicle

Human Follicle Classification
Follicle Class	Alternate nomenclature	Type	Number of Cells	Size (diameter µm)
Secondary	small antral large antral	6 7	3001 - 500 501 - 1000	500 1000 - 6000

Human Ovarian Follicle Classification
Class	Alternate nomenclature	Type	Number of Cells	Size (diameter µm)	Size ultrasound (mm)
primordial follicle	small	1, 2, 3	25	less than 50
primary follicle	preantral	4 5	26 - 100 101 - 300	up to 200
secondary follicle	antral small antral large antral	6 7	3001 - 500 501 - 1000	500 1000 - 6000	less than 18
preovulatory follicle	Graafian	8	greater than 1000	greater than 6000	18 – 28
Links: ovary | oocyte | menstrual cycle

Preovulatory Follicle

From the cohort of secondary follicles, in the late luteal phase of the previous menstrual cycle, a dominant follicle now grows, the "Graafian follicle". The follicle growth rate is about 2 mm per day, achieving a preovulatory diameter between 18 to 28 mm as measured by ultrasound. Ovulation is triggered by a surge of pituitary luteinizing hormone (LH) about 36 hours before follicle release.

Human Follicle Classification
Follicle Class	Alternate nomenclature	Type	Number of Cells	Size (diameter µm)
Preovulatory	Graafian	8	greater than 1000	greater than 6000

Human Ovarian Follicle Classification
Class	Alternate nomenclature	Type	Number of Cells	Size (diameter µm)	Size ultrasound (mm)
primordial follicle	small	1, 2, 3	25	less than 50
primary follicle	preantral	4 5	26 - 100 101 - 300	up to 200
secondary follicle	antral small antral large antral	6 7	3001 - 500 501 - 1000	500 1000 - 6000	less than 18
preovulatory follicle	Graafian	8	greater than 1000	greater than 6000	18 – 28
Links: ovary | oocyte | menstrual cycle

Atresia

At any one time the majority of follicles are destined not to complete maturation and at any stage (from type 4-7) degeneration of the follicle can occur. Cells die by apoptosis.

Follicle Growth

Graph shows species comparison in follicle size growth (diameter) at different stages of follicle development. (See also Oocyte size graph)

Human Ovarian Follicle Classification
Class	Alternate nomenclature	Type	Number of Cells	Size (diameter µm)	Size ultrasound (mm)
primordial follicle	small	1, 2, 3	25	less than 50
primary follicle	preantral	4 5	26 - 100 101 - 300	up to 200
secondary follicle	antral small antral large antral	6 7	3001 - 500 501 - 1000	500 1000 - 6000	less than 18
preovulatory follicle	Graafian	8	greater than 1000	greater than 6000	18 – 28
Links: ovary | oocyte | menstrual cycle

Follicle Factors

Ovarian developmental genes

There are both external endocrine factors and internal follicle factors that can influence the development and atresia of ovarian follicles.

External Factors

Leutenizing Hormone (LH)

• from the anterior pituitary
• stimulate the theca interna to synthesize and secrete androgens (androstendione) transported to granulosa cells
• granulosa cells process initially into testosterone and then by aromatase into estrogen (estradiol)

Follicle-stimulating hormone (FSH)

• from the anterior pituitary
• initiates follicle growth through the granulosa cells
• involved in selecting the most advanced (sensitive) follicle to proceed to ovulation

Internal Factors

Oocyte Factors

• Growth Differentiation Factor-9 (GDF-9) - involved in the differentiation of theca cells during this early stage of follicular development OMIM 601918
• Bone morphogenetic protein 15 (BMP15)
• Fibroblast growth factor 8B (FGF8B)

Granulosal Factor(s)

• stimulates the recruitment of theca cells from cortical stromal cells

Thecal Factor(s)

• appear to be several inhibitors of apoptotic cell death
• Epidermal growth factor (EGF)
• Transforming growth factor alpha (TGF-α)
• keratinocyte growth factor (KGF)
• hepatocyte growth factor (HGF)
• Bone morphogenetic protein 7 (BMP-7) also known as osteogenic protein-1 or OP-1

Molecular

Mammalian Sexual Development Genes
Gene (OMIM)	Protein Function	Gonad Phenotype of Null Mice	Human Syndrome
Ovary-determining pathway
Wnt4	Signaling molecule	Müllerian duct agenesis, testosterone synthesis, and coelomic vessel formation	XY female (GOF)
FoxL2	Transcription factor	Premature ovarian failure	BPES
Dax1	Nuclear receptor	XY sex reversal (GOF)	XY sex reversal (GOF)
RSPO1	Signaling molecule	XX sex reversal (LOF)	XX sex reversal (LOF)
Table Legend
	BPES - blepharophimosis-ptosis-epicanthus inversus syndrome GOF - gain-of-function mutation LOF - loss-of-function mutation ND - not determined WAGR - Wilms' tumor-aniridia-genitourinary malformations-mental retardation		a No mutations in human sexual disorders identified to date. b Candidate gene for 9p deletion, XY sex reversal.
Table modified from

Ovary Growth

Table below is from historic data (1912) from measurement of human histological materials.

Table showing the Growth of the Ovary
Vertex-breech length	Greatest diam. of head	Right Ovary		Left Ovary		Comparison between
		Breadth	Length	Breadth	Length	Length		Breadth
						R.	L.	R.	L.
50.0	42.6	0.9	1.9	0.9	2.5	..	+	—	—
125.0	123.0	1.2	5.9	1.5	4.1	+	..	..	+
138.0	115.0	1.6	5.0	2.0	5.0	—	—	..	+
156.0	131.0	1.9	7.2	2.0	7.1	+	..	..	+
173.0	163.5	3.0	9.0	...	...	..	..	..	..
190.0	175.0	2.9	7.7	2.1	7.8	..	+	+	..
223.0	162.0	2.9	10.5	3.0	9.1	+	..	..	+
235.0	190.0	4.2	10.0	3.8	12.0	..	+	+	..
260.0	213.0	3.6	11.1	4.0	11.4	..	+	..	+
272.0	213.0	3.0	10.0	3.5	9.2	+	..	..	+
305.0	238.0	3.0	9.9	3.9	10.9	..	+	..	+
347.0	...	3.5	10.8	4.9	8.5	+	..	..	+
355.0	273.0	4.0	14.0	5.2	9.9	+	..	..	+
386.0	324.0	5.1	11.5	3.0	9.9	+	..	+	..
402.0	301.0	5.05	10.5	3.0	12.0	..	+	+	..
3 weeks	...	5.0	17.0	5.0	14.0	+	..	—	—
6 weeks	...	7.5	15.0	7.0	14.7	+	..	+	..
6 weeks	...	7.0	18.0	8.0	17.0	+	..	..	+
10 weeks	...	...	14.0	...	16.0	+	..	—	—
2 months	...	6.0	14.5	4.0	13.0	+	..	+	..
3 months	...	6.0	15.5	5.0	14.7	+	..	+	..
7 months	...	5.9	15.5	4.5	18.1	..	+	+	..
15 months	...	9.0	18.0	9.0	19.5	+	..	—	—
I.75 years	...	7.0	20.0	8.5	15.0	+	..	..	+
4 years	...	10.0	27.0	12.7	23.2	+	..	..	+
5.5 years	...	11.1	29.0	9.1	26.1	+	..	+	..
14 years	...	11.9	26.5	12.0	29.5	..	+	..	+
The measurements are all given in millimeters, breech length is measured along the nape and the back.
Links: 1912 Ovary Growth | Table Ovary Growth Table | Collapsible Table | Ovary Development

Table showing the Growth of the Ovary
Vertex-breech length	Greatest diam. of head	Right Ovary		Left Ovary		Comparison between
		Breadth	Length	Breadth	Length	Length		Breadth
						R.	L.	R.	L.
50.0	42.6	0.9	1.9	0.9	2.5	..	+	—	—
125.0	123.0	1.2	5.9	1.5	4.1	+	..	..	+
138.0	115.0	1.6	5.0	2.0	5.0	—	—	..	+
156.0	131.0	1.9	7.2	2.0	7.1	+	..	..	+
173.0	163.5	3.0	9.0	...	...	..	..	..	..
190.0	175.0	2.9	7.7	2.1	7.8	..	+	+	..
223.0	162.0	2.9	10.5	3.0	9.1	+	..	..	+
235.0	190.0	4.2	10.0	3.8	12.0	..	+	+	..
260.0	213.0	3.6	11.1	4.0	11.4	..	+	..	+
272.0	213.0	3.0	10.0	3.5	9.2	+	..	..	+
305.0	238.0	3.0	9.9	3.9	10.9	..	+	..	+
347.0	...	3.5	10.8	4.9	8.5	+	..	..	+
355.0	273.0	4.0	14.0	5.2	9.9	+	..	..	+
386.0	324.0	5.1	11.5	3.0	9.9	+	..	+	..
402.0	301.0	5.05	10.5	3.0	12.0	..	+	+	..
3 weeks	...	5.0	17.0	5.0	14.0	+	..	—	—
6 weeks	...	7.5	15.0	7.0	14.7	+	..	+	..
6 weeks	...	7.0	18.0	8.0	17.0	+	..	..	+
10 weeks	...	...	14.0	...	16.0	+	..	—	—
2 months	...	6.0	14.5	4.0	13.0	+	..	+	..
3 months	...	6.0	15.5	5.0	14.7	+	..	+	..
7 months	...	5.9	15.5	4.5	18.1	..	+	+	..
15 months	...	9.0	18.0	9.0	19.5	+	..	—	—
I.75 years	...	7.0	20.0	8.5	15.0	+	..	..	+
4 years	...	10.0	27.0	12.7	23.2	+	..	..	+
5.5 years	...	11.1	29.0	9.1	26.1	+	..	+	..
14 years	...	11.9	26.5	12.0	29.5	..	+	..	+
The measurements are all given in millimeters, breech length is measured along the nape and the back.
Reference: Felix W. The development of the urinogenital organs. In Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia. pp 752-979.
Links: 1912 Ovary Growth | Table Ovary Growth Table | Collapsible Table | Ovary Development

Postnatal Growth

Human ovary postnatal volume growth

Corpus Luteum

Human ovary with corpus luteum (white ring).

The corpus luteum (Latin, corpus = body, luteum = yellow) develops from the remains of Graffian follicle after ovulation. Functions as an endocrine organ (produce progesterone and oestrogens) supporting pregnancy and preventing menstruation (loss of the endometrial lining). Formed during the luteal phase (secretory phase) of the menstrual cycle by proliferation of both follicular granulosa cells (granulosa lutein cells) and thecal cells (theca lutein cells), which together interact to produce progesterone and oestrogens.

Peak luteal function during the menstrual cycle, determined by maximum luteal area, progesterone concentration and estradiol concentration, is observed about 6 days following ovulation.

If fertilization and pregnancy does not occur, the corpus luteum degenerates to form the corpus albicans.

History

• Regnier de Graaf (1641 – 1673) was the first observer in the ovary of a cow as a yellow structure, the yellow colour was caused by accumulation of steroidal hormones.
• Ludwig Fraenkel (1870 - 1951) first identified the endocrine function of the corpus luteum.

Embryo Virtual Slide

Human Ovary and Corpus Luteum

‎‎Mobile | Desktop | Original

Ovary | Embryo Slides

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  Human corpus luteum (large image)

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  Human corpus luteum (small image)

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  Corpus luteum histology

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  Corpus luteum histology

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  Corpus luteum lutein cells histology

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  Human corpus luteum (light and electron micrograph)

Corpus Albicans

Human ovary with corpus albicans (white arrow).

Corpus albicans histology

(corpora albicantia) (Latin, corpus = body, albicans = whitish) The histological structure formed by luteolysis of the corpus luteum in the ovary. If implantation does not occur and the hormone hCG is not released the corpus luteum degenerates and the structure is white, not yellow, because of the absence of steroid hormone synthesis/accumulation.

Animal Models

Bovine Ovary

Links: Bovine Development

Ovarian Development Model A - The development of the ovary commences at the mesonephric surface epithelium (yellow cells) in the location of the future gonadal ridge. B - Some mesonephric surface epithelial cells change phenotype into GREL (Gonadal Ridge Epithelial-Like) cells (yellow-blue cells). C - The GREL cells proliferate and the basal lamina underlying the mesonephric surface epithelium breaks down allowing stromal cells (green) to penetrate into the gonadal ridge. D - GREL cells continue to proliferate and PGCs (grey) migrate into the ridge between the GREL cells. Mesonephric stroma including vasculature (red) continues to penetrate and expand in the ovary. E - Oogonia proliferate and stroma penetrates further towards the ovarian surface enclosing oogonia and GREL cells into ovigerous cords. The cords are surrounded by a basal lamina at their interface with stroma, but are open to the ovarian surface. Stromal areas including those between the ovigerous cords contain capillaries. F - A compartmentalization into cortex and medulla becomes obvious. The cortex is characterised by alternating areas of ovigerous cords and stroma, whereas the medulla is formed by stromal cells, vasculature and tubules originating from the mesonephros (rete ovarii). Once stroma penetrates below the cells on the surface it spreads laterally. The GREL cells at the surface are then aligned by a basal lamina at their interface with the stroma and begin to differentiate into typical ovarian surface epithelium (yellow cells). Some germ cells at the surface are also compartmentalized to the surface as stroma expands below it. G - Ovigerous cords are partitioned into smaller cords and eventually into follicles. These contain GREL cells that form granulosa cells (blue cells) and oogonia that form oocytes. The first primordial follicles appear in the inner cortex-medulla region, surrounded by a basal lamina. A now fully intact basal lamina underlies multiple layers of surface epithelial cells. H - At the final stage the surface epithelium becomes mostly single-layered and a tunica albuginea, densely packed with fibres, develops from the stroma below the surface epithelial basal lamina. Some primordial follicles become activated and commence development into primary and preantral follicles.

Histology

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  Ovary histology (monkey) showing the tunica albuginea and primordial follicles x20

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  Tunica albuginea, Germinal epithelium x40

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  Primary follicle, primordial follicle, oocyte, x40

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  Secondary follicle, cumulus oophorus, zona pelucida, granulosa cells, oocyte x20

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  Corpus luteum, theca lutein cells, granulosa lutein cells, Loupe

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  Corpus luteum, theca lutein cells, granulosa lutein cells, x10

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  Corpus luteum, theca lutein cells, granulosa lutein cells, x40

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  Corpus albicans, primary follicle, primordial follicle, granulosa cells, oocyte x20

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  Ovary histology (cat) overview showing cortical follicle development stages

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  Ovary histology (cat) showing follicle stages

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  Ovary histology (monkey) showing the primordial and primary follicle

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  Ovary histology (monkey) showing the secondary follicle

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  Ovary histology (monkey) showing primary follicle, primordial follicle, oocyte histology

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  Ovary histology (monkey) showing the primordial follicles

Ovary histology: Tunica Albuginea x20 | Tunica albuginea, Germinal epithelium x40 | Primary follicle, primordial follicle, oocyte, x40 | Secondary follicle, cumulus oophorus, zona pelucida, granulosa cells, oocyte x20 | Corpus luteum, theca lutein cells, granulosa lutein cells, Loupe | Corpus luteum, theca lutein cells, granulosa lutein cells, x10 | Corpus luteum, theca lutein cells, granulosa lutein cells, x40 | Corpus albicans, primary follicle, primordial follicle, granulosa cells, oocyte x20 | Menstrual Cycle | Ovary Development

Germinal Epithelium

Germinal epithelium and tunica albuginea (monkey ovary)

(germinal epithelium of Waldeyer) A layer of simple cuboidal epithelium covering the ovary. Arising from mesoderm and related to the mesothelium of the peritoneum.

This is a historic misnomer, based upon Waldeyer's (1870) hypothesis that germ cells arise from this coelomic epithelium (More? Gray Fig 1113). This epithelium has no role in the formation of the oocyte, formed developmentally from primordial germ cells migrating into the ovary.

In contrast, a similar named "epithelial" tissue layer is found in male genital system within the seminiferous tubules. This is the layer where the spermatozoa develop.

Tunica Albuginea

A dense connective tissue layer lying near the ovary surface, that is covered by a layer of simple cuboidal epithelium. A similar connective tissue layer is found in male genital system, as fibrous envelope covering the penis corpora cavernosa and corpus spongiosum.

Abnormalities

See also Genital System - Abnormalities

Female Infertility Genes

Selected Female Infertility Genes

Gene abbreviation	Name	Gene Location	Online Mendelian Inheritance in Man (OMIM)	HUGO Gene Nomenclature Committee (HGNC)	GeneCards (GCID)	Diagnosis
BMP15	Bone morphogenetic protein 15	Xp11.22	300247	1068	GC0XP050910	Primary ovarian insufficiency
CLPP	Caseinolytic mitochondrial matrix peptidase proteolytic subunit	19p13.3	601119	2084	GC19P006369	Primary ovarian insufficiency
EIF2B2	Eukaryotic translation initiation factor 2B subunit beta	14q24.3	606454	3258	GC14P075002	Primary ovarian insufficiency
FIGLA	Folliculogenesis-specific BHLH transcription factor	2p13.3	608697	24669	GC02M070741	Primary ovarian insufficiency
FMR1	Fragile X mental retardation 1	Xq27.3	309550	3775	GC0XP147912	Primary ovarian insufficiency
FOXL2	Forkhead box L2	3q22.3	605597	1092	GC03M138944	Primary ovarian insufficiency
FSHR	Follicle stimulating hormone receptor	2p16.3	136435	3969	GC02M048866	Primary ovarian insufficiency
GALT	Galactose-1-phosphate uridylyltransferase	9p13.3	606999	4135	GC09P034636	Primary ovarian insufficiency
GFD9	Growth differentiation factor 9	5q31.1	601918	4224	GC05M132861	Primary ovarian insufficiency
HARS2	Histidyl-TRNA synthetase 2, mitochondrial	5q31.3	600783	4817	GC05P141975	Primary ovarian insufficiency
HFM1	HFM1, ATP-dependent DNA helicase homolog	1p22.2	615684	20193	GC01M091260	Primary ovarian insufficiency
HSD17B4	Hydroxysteroid 17-beta dehydrogenase 4	5q23.1	601860	5213	GC05P119452	Primary ovarian insufficiency
LARS2	Leucyl-TRNA synthetase 2, mitochondrial	3p21.31	604544	17095	GC03P045405	Primary ovarian insufficiency
LHCGR	Luteinizing hormone/choriogonadotropin receptor	2p16.3	152790	6585	GC02M048647	Primary ovarian insufficiency
LHX8	LIM homeobox 8	1p31.1	604425	28838	GC01P075128	Primary ovarian insufficiency
MCM8	Minichromosome maintenance 8 homologous recombination repair factor	20p12.3	608187	16147	GC20P005926	Primary ovarian insufficiency
MCM9	Minichromosome maintenance 9 homologous recombination repair factor	6q22.31	610098	21484	GC06M118813	Primary ovarian insufficiency
NOBOX	NOBOX oogenesis homeobox	7q35	610934	22448	GC07M144397	Primary ovarian insufficiency
NOG	Noggin	17q22	602991	7866	GC17P056593	Primary ovarian insufficiency
PMM2	Phosphomannomutase 2	16p13.2	601785	9115	GC16P008788	Primary ovarian insufficiency
POLG	DNA polymerase gamma, catalytic subunit	15q26.1	174763	9179	GC15M089316	Primary ovarian insufficiency
REC8	REC8 meiotic recombination protein	14q12	608193	16879	GC14P024171	Primary ovarian insufficiency
SMC1B	Structural maintenance of chromosomes 1B	22q13.31	608685	11112	GC22M045344	Primary ovarian insufficiency
SOHLH1	Spermatogenesis and oogenesis-specific basic helix–loop–helix 1	9q34.3	610224	27845	GC09M135693	Primary ovarian insufficiency
STAG3	Stromal antigen 3	7q22.1	{{Chr 608489	11356	GC07P100177	Primary ovarian insufficiency
SYCE1	Synaptonemal Complex Central Element Protein 1	10q26.3	611486	28852	GC10M133553	Primary ovarian insufficiency
TLE6	Transducin-like enhancer of split 6	19p13.3	612399	30788	GC19P002976	Embryonic lethalithy
TUBB8	Tubulin beta 8 Class VIII	10p15.3	616768	20773	GC10M000048	Oocyte maturation arrest
TWNK	Twinkle MtDNA helicase	10q24.31	606075	1160	GC10P100991	Primary ovarian insufficiency
Table data source (table 1)    Links: fertilization | oocyte | ovary | | Female Infertility Genes | spermatozoa | testis | Male Infertility Genes | Genetic Abnormalities | ART  Primary ovarian insufficiency - depletion or dysfunction of ovarian follicles with cessation of menses before age 40 years.  Oocyte maturation arrest - arrest of human oocytes may occur at different stages of meiosis.

International Classification of Diseases

ICD-11 5A80 Ovarian dysfunction

5A80.0 Clinical hyperandrogenism - Presence of hirsutism, acne or androgenic alopecia (scalp hair loss in women) 5A80.1 Polycystic ovary syndrome 5A80.2 Polycystic ovary - Ovary with increased size (> 7 mL) and stromal volume, and with increased number of follicles (12 or more measuring 2-0 mm in diameter), that may be present in women with PCOS, but also in women with normal ovulatory function and normal fertility (unilaterally or bilaterally). 5A80.3 Anovulation 5A80.4 Oligo-ovulation - Oligo-ovulation (less than 4 ovulations in the last 12 months) not related to described categories of endocrine dysfunction. Excludes anovulation related to PCOS, hyperprolactinemia or amenorrhea. 5A80.5 Diminished ovarian reserve - Ovaries with lower number of oocytes than expected for female chronologic age, marked by biochemical abnormalities (increased serum FSH levels, decreased serum AMH levels) and/or ultrasound findings (low antral follicle count) associated with ovarian ageing, reduced response to ovarian stimulation, and female infertility. GA30.6 Premature ovarian failure - Menopause occurring spontaneously before 40 years of age, generally resulting in secondary amenorrhea although some women may exhibit intermittent ovarian function and ovulation, with a minority conceiving and delivering a pregnancy. POF/POI occurs mostly without a known cause, but can be caused by the following conditions: numerical and structural chromosomal abnormalities, Fragile X (FMR1) premutations, autoimmune disorders, radiation therapy, chemotherapy, galactosemia, and other rare enzyme defects or mutations. To be subdivided in 4 categories according to cause: congenital, acquired, iatrogenic and unknown

Polycystic Ovary Syndrome

Mouse ovary normal and polycystic ovary syndrome model.

 ICD-11 5A80.1 Polycystic ovary syndrome | 5A80.2 Polycystic ovary - Ovary with increased size (> 7 mL) and stromal volume, and with increased number of follicles (12 or more measuring 2-0 mm in diameter), that may be present in women with PCOS, but also in women with normal ovulatory function and normal fertility (unilaterally or bilaterally).

Polycystic ovary syndrome (PCOS) or Stein-Leventhal syndrome (1930s researchers) clinical term for a metabolic hormone syndrome leading to anovulation and with many other symptoms (hyperandrogenism, insulin resistance) and is one of the most common forms of female infertility, see reviews. Using the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria, about 15% - 20% of women suffer from this disease. Ovarian cysts arise through incomplete follicular development or failure of ovulation (anovulation). A range of drugs has been used to induce ovulation in these women and more recently in vitro maturation (IVM) has also been suggested as a possible future technique. Androgen has been recently identified as a key mediator in the development of polycystic ovary syndrome.

Recently in 2018 an Australian-led PCOS international evidence-based guideline for the diagnosis and management of polycystic ovary syndrome (PCOS) was developed for health professionals and consumers.

In December 2012, the NIH held a workshop on "Evidence-based Methodology on Polycystic Ovary Syndrome". PCOS is a common disorder affecting 5 million women of reproductive-age in the United States. Symptoms include: irregular or no menstrual periods in women of reproductive age (ovulatory dysfunction), acne, weight gain, excess hair growth on the face and body (hirsutism), thinning scalp hair, ovarian cysts (polycystic ovarian morphology) and mental health problems.

One key workshop finding was that the name "Polycystic Ovary Syndrome" is inappropriate for defining the condition and should be renamed to reflect the complex metabolic, hypothalamic, pituitary, ovarian, and adrenal interactions that characterize the syndrome and their reproductive implications.

• Androgen Excess + Ovulatory Dysfunction
• Androgen Excess + Polycystic Ovarian Morphology
• Ovulatory Dysfunction + Polycystic Ovarian Morphology
• Androgen Excess + Ovulatory Dysfunction + Polycystic Ovarian Morphology

Recurrent pregnancy loss also occurs in about 50% of total pregnancies with polycystic ovary syndrome.

A recent study in the Han Chinese population identified associations between PCOS and three genetic loci: 2p16.3, 2p21 and 9q33.3.

Introduction to PCOS

<html5media width="480" height="360">https://www.youtube.com/embed/NhyYZCBq5A8</html5media>

Links: menstrual cycle | genital abnormalities | endocrine abnormalities | 2012 NIH Workshop on PCOS | 2011 Australia Guideline assessment and management PCOS | OMIM 184700]

Premature Ovarian Failure

Premature Ovarian Failure (POF) a clinical term describes the absence of normal ovarian function due to the depletion of the primordial follicle pool before 40 years of age a range of factors (autoimmune, iatrogenic, infections, genetic defects). Primary ovarian insufficiency (POI) occurs in approximately 1% of women below 40 years of age.

Premature Ovarian Failure (POF) can be primary or secondary based on puberty.

• primary - absence of puberty, development and primary amenorrhea, generally caused by ovarian dysgenesis (45XO, Turner syndrome, Monosomy X).
• secondary - normal puberty, usually present with the later disappearance of menstrual cycles.

Search PubMed: Premature Ovarian Failure

Ovarian Cancer

Ovarian cancer (Template:ICD–10 C56) is a major cause of death in the postnatal female population. Both BRCA1 and BRCA2 genes are high-risk genes of ovarian cancer. A recent mouse study has also identified a population of stem cells located at the hilum region of the ovary that are prone to epithelial ovarian cancer.

In Australia, ovarian cancer was in 2014 the 8th most commonly diagnosed cancer among females and 2018 estimate is that it will become the 10th most commonly diagnosed cancer among females.

Luteoma of Pregnancy

Luteoma of pregnancy is a rare non-neoplastic tumor-like mass of the ovary that emerges during pregnancy and regresses spontaneously after delivery. Luteomas can be hormonally active producing androgens that can result in maternal and fetal hirsutism and virilization.

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  Abnormal - Luteoma of pregnancy

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  Abnormal - Luteoma of pregnancy

Image: Dr Ed Uthman (Houston, Texas) - other pathology images

References

Reviews

Cox E & Whitten R. (2018). Embryology, Ovarian Follicle Development. , , . PMID: 30335333

Escobar-Morreale HF. (2018). Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol , 14, 270-284. PMID: 29569621 DOI.

Nef S & Vassalli JD. (2009). Complementary pathways in mammalian female sex determination. J. Biol. , 8, 74. PMID: 19735582 DOI.

Hultén MA, Patel S, Jonasson J & Iwarsson E. (2010). On the origin of the maternal age effect in trisomy 21 Down syndrome: the Oocyte Mosaicism Selection model. Reproduction , 139, 1-9. PMID: 19755486 DOI.

Articles

Lin HA, Dutta R, Mandal S, Kind A, Schnieke A & Razansky D. (2016). Advancing ovarian folliculometry with selective plane illumination microscopy. Sci Rep , 6, 38057. PMID: 27905503 DOI.

Geber S, Megale R, Vale F, Lanna AM & Cabral AC. (2012). Variation in ovarian follicle density during human fetal development. J. Assist. Reprod. Genet. , 29, 969-72. PMID: 22710858 DOI.

Duffin K, Bayne RA, Childs AJ, Collins C & Anderson RA. (2009). The forkhead transcription factor FOXL2 is expressed in somatic cells of the human ovary prior to follicle formation. Mol. Hum. Reprod. , 15, 771-7. PMID: 19706741 DOI.

Dontchev N. (1971). [The prenatal development of the human ovary]. Arch Anat Histol Embryol , 54, 183-90. PMID: 4950043

Search Pubmed

Search Pubmed: Ovary Development | Follicle Development | Follicle Atresia

Books

Leung P. and Adashi E. The Ovary (2019) 3rd Edn eBook ISBN: 9780128132104 Hardcover ISBN: 9780128132098 Academic Press.

1. The Ovarian Follicular Apparatus: Operational Characteristics
2. Oocyte Maturation and Ovulation
3. The Corpus Luteum
4. Novel Experimental Models
5. Human Ovarian Pathophysiology: Select Aspects
6. Human Ovarian Cancer

Gilbert SF. Developmental Biology. (2000) 6th edn. Sunderland (MA): Sinauer Associates.

1. oogenesis

Additional Images

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  Human ovary follicle basement membrane

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  Human ovary non-growing follicle model

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  Model of human fetal ovarian cord development

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  Original calculations of human ovary oocyte number

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  The ovary and uterus

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  The female hypothalamic–pituitary–gonadal axis

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  Mouse - gonadal supporting cell development

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  Human - ovary age primary follicle numbers

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  Human fetal ovary - FOXL2 expression

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  Model of pathways for formation of primary follicles in adult human ovaries

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  Mouse model of ovarian cord formation

Historic Images

Historic Disclaimer - information about historic embryology pages

Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

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Terms

Oocyte Development

oocyte

Note there are additional specific term glossaries available listed at bottom of this table.

• antral follicle - (secondary) the stage following preantral in the decription of the sequence ovarian follicle development.

• antrum - (L. a cave), cavity; a nearly-closed cavity or bulge. In the ovary this refers to the follicular fluid-filled space within the follicle.

• atretic follicle - An ovarian follicle that fails to mature and degenerates. Also called "atresia" refering to the process of degeneration of the ovarian follicle. This process can occur at any stage of follicle development (folliculogenesis).

• clomiphene citrate - drug taken orally to promote the process of follicle/egg maturation.

• COCs - (cumulus-oocyte complexes) term used in Assisted Reproductive Technology to describe the ovulated Graafian follicle consisting of the oocyte surrounded by a packed layers of cumulus cells.

• corona radiata - Layer of follicle cells of cumulus oophorus remaining directly attached to zona pellucida of the oocyte. These cells communicate with the oocyte through the zone pellucida, also called granulosa cells.

• corpus albicans - (L. corpus = body, L. albicans = whitish); a degenerating corpus luteum in ovary.

• corpus luteum - (L. corpus = body, L. luteum = yellow) The remains of the ovulating ovarian follicle after ovulation, that acts as the initial endocrine organ supporting pregnancy and preventing menstruation (loss of the endometrial lining). de Graaf first observed it in the ovary of a cow as a yellow structure.

• cortical - (L. corticalis) at the outside (like the bark of a tree), usually combined with medulla meaning the core.

• cumulus oophorus - (L. cumulus = a little mound G. oon = egg + phorus = bearing); part of the wall of an ovarian follicle surrounding and carrying the ovum (oocyte).

• dictyate arrest - (prophase arrest) the oocyte meiosis state before puberty resumed with a surge of pituitary luteinizing hormone.

• first polar body - a small cytoplasmic exclusion body contains the excess DNA from the oocyte meiosis formed during meiosis 1.

• follicle - (L. folliculus = little bag,dim. of L. follis). A structure which develops in the ovary and contains a developing egg (oocyte).

• follicle stimulating hormone - (FSH, gonadotropin) A glycoprotein hormone secreted by anterior pituitary (adenohypophysis gonadotrophs, a subgroup of basophilic cells) and acts on gametogenesis and other systems in both males and females. Females, FSH acts on the ovary to stimulate follicle development. Males, acts on the testis Sertoli cells to increase androgen-binding protein (ABP) that binds androgens and has a role in spermatogenesis. pituitary

• follicular fluid - the fluid found in the antrum of a secondary follicle. Secreted by cells in the wall of the follicle. This fluid is released along with the oocyte at ovulation.

• germinal epithelium - cellular component covering surface of ovary, it is continuous with mesothelium covering mesovarium. Note that it is a historical misnomer, as it is not the actual site of germ cell formation.

• Graafian follicle - named after Regnier de Graaf (1641-1673), an historic Dutch physician embryologist who studied pregnancy using rabbits.

• granulosa cells - the supporting cells that surround the developing egg within the follicle thecal layers.

• homologs - maternal and paternal homologous chromosomes.

• Izumo1 - a protein located on the equatorial segment of acrosome-reacted spermatozoa recognizes its receptor Juno, on the oocyte surface, for plasma membrane binding and fusion. Named for a Japanese shrine dedicated to marriage. OMIM609278

• Juno - (folate receptor-δ; FOLR-δ) a glycophosphatidylinositol (GPI)-anchored, cysteine-rich glycoprotein on the oocyte surface for fertilisation that is the receptor of Izumo1 on the spermatozoa, for plasma membrane binding and fusion. OMIM615737

• luteinizing hormone - (LH, gonadotropin, lutropin, Interstitial Cell Stimulating Hormone, ICSH) glycoprotein hormone releasd from anterior pituitary hormone that acts on the gonad and has a role in male and female reproduction. Female, LH triggers ovulation (release of the oocyte). Male, LH stimulates testis interstital cell (Leydig cell) production of testosterone. Have been used clinically in humans for the treatment of female infertility.

• meiosis - oocyte reductive (diploid to haploid) cell division, with 1 round of DNA replication is followed by 2 rounds of chromosome segregation. The process beginning in the fetus and only completed at fertilization.

• mesovarium - mesentry of the ovary formed from a fold of the broad ligament that attaches the ovary.

• medullary - (L. medius = in the middle) relating to the medulla; pith, marrow, inner portion of an organ. Usually combined with cortex (cortical) meaning the outer layer.

• oocyte - (Greek, oo = egg, ovum) The term used to describe the haploid egg or ovum formed within the ovary (female gonad) and released to enter the uterine tube and be transported to the uterus. The mature oocyte is the cell released from the ovary during ovulation.

• oocyte retrieval - (egg retrieval) A clinical in vitro fertilization (IVF) procedure to collect the eggs contained in the ovarian follicles.

• oogenesis - (Greek, oo = egg + genesis = origin, creation, generation) process of diploid oogonia division and differentiation into an haploid oocyte (egg) within the ovary (female gonad). Mammalian meiosis will only be completed within the oocyte if fertilization occurs.

• oogonia - (Greek, oo = egg) diploid germ cells within the ovary (female gonad) which provide the primary oocytes for oocyte (egg) formation. In humans, all oogonia form primary oocytes within the ovary before birth.

• oolemma - (zona pellucida, vitelline membrane).

• oophorus - (Greek, oo = egg + phorus = carrying, egg-bearing) cumulus oophorus, used to describe the granulosa cells within the follicle that tether or link the oocyte to the wall of the follicle.

• ovarian reserve - Clinical term for the number of oocytes (non-growing follicles) available for possible fertilization at the different times during female reproductive life. A blood test for Anti-Mullerian Hormone (AMH) levels is used clinically as a measure of the ovarian reserve. human graph

• ovastacin - an oocyte released enzyme following fertilization that cleaves ZP2 protein to prevent polyspermy.

• ovulation - release of the oocyte from the mature follicle. In humans generally a single oocyte is released from a cohort of several maturing follicles.

• ovum - oocyte, note that historically this same term was also used to describe the early stages following fertilisation.

• polar body - small cytoplasmic exclusion body contains the excess DNA from the oocyte meiosis reductive division. The first polar body formed during meiosis 1, the second and sometimes third polar bodies are formed from meiosis 2 at fertilization.

• polyspermy - abnormal fertilization by more that a single spermatozoa, may generate a hydatidiform mole.

• preantral follicle - (primary) the stage following primordial in the description of the sequence ovarian follicle development.

• primary follicle - (preantral) the stage following primordial in the description of the sequence ovarian follicle development.

• primordial follicle - the first stage in the description of the sequence ovarian follicle development. Present in the ovary from birth, located in the stroma of the ovary cortex beneath the tunica albuginea. The primordial follicle is the oocyte and the surrounding follicular cells.

• primordial germ cell - oocyte present in the primordial follicle ovary from birth, located in the stroma of the ovary cortex beneath the tunica albuginea. The primordial follicle is the oocyte and the surrounding follicular cells.

• second polar body - a small cytoplasmic exclusion body contains the excess DNA from the oocyte formed during meiosis 2 at fertilization.

• secondary follicles - the stage following primary in the description of the sequence ovarian follicle development.

• stromal cells - in the ovary, cells surrounding the developing follicle that form a connective tissue sheath (theca folliculi). This layer then differentiates into 2 layers (theca interna, theca externa). This region is richly vascularized and involved in hormone secretion.

• superovulation therapy - a fertility drug treatement (oral clomiphene citrate and/or injectable FSH with or without LH) aimed at stimulating development/release of more than one follicle during a single menstrual cycle.

• tertiary follicle - (preovulatory, Graffian) the stage following secondary in the description of the sequence ovarian follicle development.

• theca folliculi - stromal cells in the ovary, cells surrounding the developing follicle that form a connective tissue sheath. This layer then differentiates into 2 layers (theca interna, theca externa). This region is vascularized and involved in hormone secretion.

• theca externa - stromal cells forming the outer layer of the theca folliculi surrounding the developing follicle. Consisting of connective tissue cells, smooth muscle and collagen fibers.

• theca interna - stromal cells forming the inner layer of the theca folliculi surrounding the developing follicle. This vascularized layer of cells respond to LH (leutenizing hormone) synthesizing and secreting androgens which are processed into estrogen.

• transzonal projection - (TZP) ovarian follicle term describing the cellular membraneous extension from the granulosa cell through the zona pellucida to the oocyte cell membrane where it forms gap junctions or adherens junctions allowing signalling and adhesion between the two cells.

• tunica albuginea - dense connective tissue layer lying near the ovary surface, a layer of simple squamous to cuboidal epithelial covers this layer. A similar named structure is found in male genital system.

• uterus - site of embryo implantation and development. Uterine wall has 3 major layers: endometrium, myometrium, and perimetrium. Endometrium can be further divided into the functional layer (shed/lost during menstruation) and basal layer (not lost during menstruation).

• zinc sparks following fertilization the oocyte releases a burst of zinc atoms in brief bursts (zinc sparks) has a role in zonal pellucida induced structural changes (hardening) along with ovastacin cleavage of ZP2 protein.

• zona hardening - following fertilization the structural changes that occur to the zona pellucida to prevents further spermatozoa binding acting as a block to polyspermy.

• zona pellucida - extracellular layer lying directly around the oocyte underneath follicular cells. Has an important role in egg development, fertilization and blastocyst development. This thick extracellular matrix consists of glcosaminoglycans and 3 glycoproteins (ZP1, ZP2, ZP3). (More? Zona pellucida)

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Cite this page: Hill, M.A. (2023, December 5) Embryology Ovary Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Ovary_Development

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G